Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review
Top Cited Papers
Open Access
- 4 February 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Environmental Research and Public Health
- Vol. 18 (4), 1464
- https://doi.org/10.3390/ijerph18041464
Abstract
Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.Keywords
This publication has 170 references indexed in Scilit:
- Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesityBMC Medicine, 2013
- Polychlorinated biphenyl (PCB) exposure in mothers and time to pregnancy in daughtersReproductive Toxicology, 2011
- Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalitiesProceedings of the National Academy of Sciences of the United States of America, 2010
- Bisphenol A exposure leads to specific microRNA alterations in placental cellsReproductive Toxicology, 2010
- Xenoestrogen-Induced Regulation of EZH2 and Histone Methylation via Estrogen Receptor Signaling to PI3K/AKTMolecular Endocrinology, 2010
- Oxidative DNA damage impairs global sperm DNA methylation in infertile menJournal of Assisted Reproduction and Genetics, 2009
- Endocrine-Disrupting Chemicals: An Endocrine Society Scientific StatementEndocrine Reviews, 2009
- Fifteen Years after “Wingspread”—Environmental Endocrine Disrupters and Human and Wildlife Health: Where We are Today and Where We Need to GoToxicological Sciences, 2008
- Role for estradiol in female-typical brain and behavioral sexual differentiationFrontiers in Neuroendocrinology, 2008
- The language of covalent histone modificationsNature, 2000